Canadian clinical trial registry

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Study Description

MEKTOVI (binimetinib) is a medicine taken by mouth that helps block certain signals in the body that make some tumors grow. In this Phase II study, the drug will be used to treat children diagnosed with Adamantinomatous Craniopharyngioma (ACP), a type of brain tumor. This tumor can be very challenging to treat, and current options like surgery and radiation can affect the patient's quality of life, especially when the tumor comes back.

Recent research shows that ACP might respond to medicines like binimetinib that block specific pathways in the body.

Up to 38 children will take binimetinib in pill form, twice a day for 4 weeks (1 cycle), and treatment could continue for up to two years. The trial will include children aged 1 to 25, some of whom have already had radiation therapy.

The goal is to see if this medicine can help control the tumor and improve their quality of life.

Inclusion Criteria

• Patients must be between 1 and 25 years old.
• Must have a confirmed Adamantinomatous Craniopharyngioma (ACP), either from a solid tumor or cyst fluid.
• Must have a measurable tumor that can be seen on scans:
  • Stratum 1: Patients whose tumor came back or got worse at least 6 months after finishing radiation therapy.
  • Stratum 2: Patients who have had surgery but have not had radiation (they may have had other treatments before).
• Patients must be able to do at least half of their usual activities, even if they use a wheelchair.
• Must have recovered from any side effects of previous treatments.
• Previous Treatments:
  • At least 7 days since the last dose of any biologic treatment (anti-tumor therapy).
  • At least 42 days since any immunotherapy (e.g. cancer vaccines).
  • At least 21 days since a monoclonal antibody treatment.
  • At least 6 months since focused radiation and no history of radiation to the whole brain/spine.
  • Corticosteroids: If on dexamethasone, the dose must be stable or reducing for at least 1 week.
  • Chemotherapy: At least 21 days since the last round of chemotherapy.
  • Surgery: At least 6 weeks since any surgery.
• Blood counts and organ function requirements must meet certain safety levels before treatment.
• Patient and/or their parent/guardian must agree to join the study by signing a consent form.

Additional inclusion and exclusion criteria may apply and will be discussed with you by the study team. 

Publications

• Foreman NK, Faestel PM, Pearson J, Disabato J, Poole M, Wilkening G, Arenson EB, Greffe B, Thorne R. Health status in 52 long-term survivors of pediatric brain tumors. J Neurooncol. 1999 Jan;41(1):47-53. doi: 10.1023/a:1006145724500.
• Goldman S, Pollack IF, Jakacki RI, Billups CA, Poussaint TY, Adesina AM, Panigrahy A, Parsons DW, Broniscer A, Robinson GW, Robison NJ, Partap S, Kilburn LB, Onar-Thomas A, Dunkel IJ, Fouladi M. Phase II study of peginterferon alpha-2b for patients with unresectable or recurrent craniopharyngiomas: a Pediatric Brain Tumor Consortium report. Neuro Oncol. 2020 Nov 26;22(11):1696-1704. doi: 10.1093/neuonc/noaa119.
• Apps JR, Carreno G, Gonzalez-Meljem JM, Haston S, Guiho R, Cooper JE, Manshaei S, Jani N, Holsken A, Pettorini B, Beynon RJ, Simpson DM, Fraser HC, Hong Y, Hallang S, Stone TJ, Virasami A, Donson AM, Jones D, Aquilina K, Spoudeas H, Joshi AR, Grundy R, Storer LCD, Korbonits M, Hilton DA, Tossell K, Thavaraj S, Ungless MA, Gil J, Buslei R, Hankinson T, Hargrave D, Goding C, Andoniadou CL, Brogan P, Jacques TS, Williams HJ, Martinez-Barbera JP. Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target. Acta Neuropathol. 2018 May;135(5):757-777. doi: 10.1007/s00401-018-1830-2. Epub 2018 Mar 14.
• Haston S, Pozzi S, Carreno G, Manshaei S, Panousopoulos L, Gonzalez-Meljem JM, Apps JR, Virasami A, Thavaraj S, Gutteridge A, Forshew T, Marais R, Brandner S, Jacques TS, Andoniadou CL, Martinez-Barbera JP. MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma. Development. 2017 Jun 15;144(12):2141-2152. doi: 10.1242/dev.150490. Epub 2017 May 15.
• Bendell JC, Javle M, Bekaii-Saab TS, Finn RS, Wainberg ZA, Laheru DA, Weekes CD, Tan BR, Khan GN, Zalupski MM, Infante JR, Jones S, Papadopoulos KP, Tolcher AW, Chavira RE, Christy-Bittel JL, Barrett E, Patnaik A. A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Br J Cancer. 2017 Feb 28;116(5):575-583. doi: 10.1038/bjc.2017.10. Epub 2017 Feb 2.
• Watanabe K, Otsu S, Hirashima Y, Morinaga R, Nishikawa K, Hisamatsu Y, Shimokata T, Inada-Inoue M, Shibata T, Takeuchi H, Watanabe T, Tokushige K, Maacke H, Shiaro K, Ando Y. A phase I study of binimetinib (MEK162) in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 Jun;77(6):1157-64. doi: 10.1007/s00280-016-3019-5. Epub 2016 Apr 12.
• Patel K, Allen J, Zagzag D, Wisoff J, Radmanesh A, Gindin T, Nicolaides T. Radiologic response to MEK inhibition in a patient with a WNT-activated craniopharyngioma. Pediatr Blood Cancer. 2021 Mar;68(3):e28753. doi: 10.1002/pbc.28753. Epub 2020 Oct 19. No abstract available.

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Study Description

This study is looking at a new drug called selumetinib to see if it works as well as (or better than) the usual treatment (drugs called carboplatin/vincristine) for children with a type of brain tumor called low grade glioma. This study is also checking if selumetinib is better for helping improve vision for children with these tumors. Selumetinib works by blocking a substance called an enzyme that the tumor cells need to grow, which can help kill them. The regular treatment uses different drugs that stop tumor cells from growing in different ways. This study will compare to see which method is better. 

Inclusion Criteria

• Patients must be >= 2 years and =< 21 years at the time of enrollment
• Patients must have neurofibromatosis type 1 (NF1), newly diagnosed or have previously diagnosed NF-1 associated LGG that has not been treated with any modality other than surgery
• Additional inclusion criteria applies for patients with optic pathway gliomas, if applicable
• Patient must meet all of the bloodwork and organ function requirements outlined in the study
• Patients with a known seizure disorder should be stable and should have not experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
• Patients must have an adequate performance status 
• Patients must have the ability to swallow whole capsules
• All patients and/or their parents or legal guardians must sign a written informed consent.

Other inclusion and exclusion criteria applies and will be discussed with you by the study team.

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Study Description

This study evaluates the safety of a type of treatment called HER2 CAR T cells (short for HER2 chimeric antigen receptor T cells). In addition to looking for side effects, we will study how well this treatment works against a brain tumor called ependymoma that has come back after treatment (recurrent) or has not responded well to treatment (progressive) in children. The HER2 CAR T cells used in this trial are made from the patient's own blood.

A new gene, called the HER2 CAR, will be inserted into patient's cells to allow them to recognize a protein on the tumor called HER2. These HER2-specific CAR T cells may be able to target and kill ependymoma tumors. This research is also studying how doable it is to provide this type of CAR T cell treatment to children being treated at different hospitals.

Inclusion Criteria

• Participants must have a diagnosis of ependymoma that is has come back or progressed.
• Patient must be ≥ 1 but ≤ 22 years of age at the time of enrollment for treatment.
• Participants must be up and about for 60% of their waking hours
• Patients must have received last dose of previous chemotherapy at least 21 days before enrollment.
• Patient must meet all organ function, bone marrow function and laboratory criteria
• The patient or parent/guardian can understand the consent and is willing to sign a written informed consent document according to institutional guidelines. Age- and developmentally appropriate assent should be obtained as required by institutional guidelines.

Additional inclusion and exclusion criteria applies and will be discussed with you by the study team.

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Study Description

(As seen on the Australian & New Zealand Childrens Haematology/Oncology Group website - https://anzchog.org/clinic-trails/connect-1903-a-pilot-and-surgical-study-of-larotrectinib-for-treatment-of-children-with-newly-diagnosed-high-grade-glioma-with-ntrk-fusion/ )

Recent research shows that a new oral tablet drug, larotrectinib, has produced promising results by shrinking some solid tumours that have an abnormal or mutated NTRK gene in adults and children.

High grade gliomas (HGG) are fast growing, aggressive brain cancers and if they recur after initial treatment, there are no effective treatment options. This study will investigate if larotrectinib alone as well as Larotrectinib  in combination with chemotherapy or radiotherapy can  be of benefit in children with high grade gliomas with the mutated NTRK gene. This international trial will study how well the drug is tolerated and its effectiveness to shrink these tumours when used alone or when given with standard chemotherapy or after radiation.

Inclusion Criteria

(As seen on the Australian & New Zealand Childrens Haematology/Oncology Group website - https://anzchog.org/clinic-trails/connect-1903-a-pilot-and-surgical-study-of-larotrectinib-for-treatment-of-children-with-newly-diagnosed-high-grade-glioma-with-ntrk-fusion/ )

• Patient must be 21 years old or younger and newly diagnosed with high grade glioma (HGG)
• The tumour must have a genetic anomaly called an NTRK fusion for the patient to qualify
• Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team

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Study Description

This study is to find the appropriate dose as well as to assess the safety and effectiveness of a drug called quizartinib for children with relapsed or refractory acute myeloid leukemia (AML) with a certain mutation called FLT3-ITD. Quizartinib is a drug designed to specifically block the FLT3 protein when it is abnormal in a leukemia cell.

Inclusion Criteria

• Children 1 month to 21 years of age
• Acute myeloid leukemia that has come back or is not responding to current treatment
• Presence of the FLT3-ITD mutation in the leukemia
• Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team.

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Study Description

VICTORY is an early phase study for patients under 25 years who have a type of brain tumor called low grade glioma (LGG) that coms back or gets worse (recurrent or progressive). To participate on this study, the LGG must have certain genetic changes called CRAF or BRAF alterations.

The study has two parts:

Phase A: We are figuring out the best dose of a combination of two medicines, vinblastine and tovorafenib. Patients will take these medicines for a certain number of months, then just tovorafenib for a few more months. Their progress will be checked regularly with scans.

Phase B: After we find the right dose in Phase A, we'll test how well the combination of these drugs works. Patients will take these medicines for a certain number of months, then just tovorafenib for a few more months. Their progress will be checked regularly with scans.

Patients will be in the study for about two years unless their tumor gets worse (disease progression), they have bad side effects or they decide to withdrawal from the study.

Inclusion Criteria

• Patients must be less than or equal to 25 years of age at the time of enrollment
• Patient and/or their parent/guardian must sign an informed consent form to be enrolled on study
• Patients must have a diagnosis of low grade glioma (LGG) with a genetic alteration called BRAF or CRAF alteration that has come back (recurrent) or not responded to previous treatment (progressive)
• Patients must have completed at least 1 other therapy prior to enrollment on this study and recovered from its effects.
• Patients must have adequate performance status (daily activities which they are able to do) 
• Must have adequate organ function in bone marrow, kidneys, liver, heart and thyroid
• Willingness of male and female patients with reproductive potential to use double effective birth control methods, defined as one used by the patient and another by his/her partner, for the duration of treatment and for 180 days following the last dose of study drug. 
• Ability to swallow tablets or liquid, or gastric access via a nasal or gastric tube.

Other inclusion and exclusion criteria may apply and will be discussed with you by the study team.

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Study Description

In this study, a drug called tocilizumab will be used to treat patients with a brain tumour called Adamantinomatous Craniopharyngioma between the ages of 1 and 25 years old. This cancer is currently treated with surgery and radiation, which can impact the quality of life for patients - instead, this drug interacts with IL-6, which is a type of protein in your body called a cytokine. By blocking the function of IL-6, this study explores if the drug is safe and effective at inducing a tumor response.

Inclusion Criteria

• Participants must be ≥ 12 months and ≤ 25 years of age at the time of study enrollment.
• Participants must have a confirmed diagnosis of adamantinomatous craniopharyngioma that has previously been treated
• Participants must be up and about at least half of their waking hours
• Must have recovered from the effects of any prior therapies
• Participants must meet the organ function and lab work requirements 
• Participants and/or their parents or legal authorized representatives must sign a written informed consent.

Other inclusion and exclusion criteria may apply and will be discussed with you by the study team. 

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Study Description

This study is to test the safety of a drug called lurbinectedin in solid tumours that have come back (relapsed) or not responded to treatment (refractory). It is conducted in 2 parts, Phase 2 will further assess this drug in participants with Ewing sarcoma specifically.

Inclusion Criteria

• Participant must meet the following age requirements:
  • Phase 1 Part 1: participants must be ≥ 2 to < 18 years of age.
  • Phase 1 Part 2: participants must be ≥ 2 to ≤ 30 years of age.
  • Phase 2: participants must be ≥ 2 to ≤ 30 years of age.
• Participant has a confirmed solid tumor (For phase 2, Ewing Sarcoma)
• The participant is up and about for more than half their waking hours
• Participant meets all lab value requirements during the screening period
• Participant weighs at least 15kg
• Must not be pregnant (if applicable), and/or must be on an acceptable birth control method 
• Must sign informed consent and agree to attending all required study assessments 

Other inclusion and exclusion criteria may apply and will be discussed with you by the study team